20,236 research outputs found

    Dynamin Is Functionally Coupled to Insulin Granule Exocytosis

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    The insulin granule integral membrane protein marker phogrin-green fluorescent protein was co-localized with insulin in Min6B1 beta-cell secretory granules but did not undergo plasma membrane translocation following glucose stimulation. Surprisingly, although expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis, it had no effect on phogringreen fluorescent protein localization in the basal or secretagogue-stimulated state. By contrast, co-expression of Dyn/K44A with human growth hormone as an insulin secretory marker resulted in a marked inhibition of human growth hormone release by glucose, KCl, and a combination of multiple secretagogues. Moreover, serial pulse depolarization stimulated an increase in cell surface capacitance that was also blocked in cells expressing Dyn/K44A. Similarly, small interference RNA-mediated knockdown of dynamin resulted in marked inhibition of glucose-stimulated insulin secretion. Together, these data suggest the presence of a selective kiss and run mechanism of insulin release. Moreover, these data indicate a coupling between endocytosis and exocytosis in the regulation of beta-cell insulin secretion

    Strategy choice in tourism supply chains for package holidays: a game-theoretic approach

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    Enterprises in a tourism supply chain usually adopt and operate two business strategies: maximizing their profits or their revenues. This paper investigates the conditions on which these strategies allow enterprises to achieve the maximum benefits in the context of entire supply chain. Several managerial implications have been derived from this theoretical research. Firstly, theme park operator, tour operators and hotel & accommodation providers obtain larger market shares and profits if they select the revenue maximization (R) strategy. Secondly, the profit maximization (P) strategy is a better strategy for both sectors when all the tour operators and all hotel & accommodation providers choose the same strategy. Finally, if both sectors could freely choose their strategies, there is market equilibrium where P-strategy and R-strategy could coexist.published_or_final_versio

    Quantitative Analysis and Skill Building in Public Administration Graduate Education

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    Trabajo de suficiencia profesionalEl presente trabajo consiste en la Implementación de control PID en un microcontrolador PIC para un esterilizador de calor seco. El diseño contempla una interfaz de usuario para poder configurar la temperatura de esterilización, según la cual el sistema regula la temperatura mediante el control PID digital y control de potencia por PWM usando como actuador una resistencia calefactora de 700 watios y como sensor de realimentación una termocupla tipo J, además controla el tiempo de esterilizado que también es configurable. Este equipo va a utilizarse para eliminar microorganismos en los materiales quirúrgicos y de laboratorio que soporten temperaturas entre los 25°C y 170°C. En tal sentido el presente informe de suficiencia profesional consta de IV capítulos : Capítulo I se detalla el problema por el cual se quiso hacer esta tesina, los objetivos la hipótesis y limitaciones y facilidades. Se quiso crear este arquetipo que fue debido a la experiencia que tuve en los trabajos en los hospitales por las dificultades que tienen los hospitales al no tener equipos de necesidad inmediata. Capítulo II se detalla la teoría para poder diseñar el esterilizador a calor como el uso de la modulación PWM ,el control PID, control encendido y apagado con respecto al control de potencia. Esta teoría ayudó en gran magnitud al análisis respectivo de los dispositivos necesarios para armar este equipo. Capítulo III se detallan los resultados obtenidos por MATLAB,PROTEUS utilizando un data logger. Se necesitó un osciloscopio de una entidad privada para la obtención de los datos necesarios en la construcción de este esterilizador a calor seco. Capítulo IV se detalla el desarrollo de los circuitos electrónicos diseñados para el esterilizador usando el PIC de la familia 16F8XX, como dispositivo de control de potencia basado en el SCR y un acondicionador de señal para el uso del sensor

    A stacked long short-term memory approach for predictive blood glucose monitoring in women with gestational diabetes mellitus

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    Gestational diabetes mellitus (GDM) is a subtype of diabetes that develops during pregnancy. Managing blood glucose (BG) within the healthy physiological range can reduce clinical complications for women with gestational diabetes. The objectives of this study are to (1) develop benchmark glucose prediction models with long short-term memory (LSTM) recurrent neural network models using time-series data collected from the GDm-Health platform, (2) compare the prediction accuracy with published results, and (3) suggest an optimized clinical review schedule with the potential to reduce the overall number of blood tests for mothers with stable and within-range glucose measurements. A total of 190,396 BG readings from 1110 patients were used for model development, validation and testing under three different prediction schemes: 7 days of BG readings to predict the next 7 or 14 days and 14 days to predict 14 days. Our results show that the optimized BG schedule based on a 7-day observational window to predict the BG of the next 14 days achieved the accuracies of the root mean square error (RMSE) = 0.958 ± 0.007, 0.876 ± 0.003, 0.898 ± 0.003, 0.622 ± 0.003, 0.814 ± 0.009 and 0.845 ± 0.005 for the after-breakfast, after-lunch, after-dinner, before-breakfast, before-lunch and before-dinner predictions, respectively. This is the first machine learning study that suggested an optimized blood glucose monitoring frequency, which is 7 days to monitor the next 14 days based on the accuracy of blood glucose prediction. Moreover, the accuracy of our proposed model based on the fingerstick blood glucose test is on par with the prediction accuracies compared with the benchmark performance of one-hour prediction models using continuous glucose monitoring (CGM) readings. In conclusion, the stacked LSTM model is a promising approach for capturing the patterns in time-series data, resulting in accurate predictions of BG levels. Using a deep learning model with routine fingerstick glucose collection is a promising, predictable and low-cost solution for BG monitoring for women with gestational diabetes

    Design and Electromagnetic Analysis of a HTS Linear Synchronous Motor

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    High temperature superconducting (HTS) linear synchronous motor (LSM) integrated with HTS magnetic levitation system, can realize self-levitation and self-guidance without any sliding friction, which will have important applications in many fields such as electromagnetic aircraft launch system, maglev transportation. This paper presents the design and electromagnetic analysis of a HTS LSM, which is levitated by a magnetic levitation system consisting of HTS bulkspermanent magnet (PM) guideways. Numerical analysis and magnetic field finite element analysis (FEA) methods are applied to analyze the thrust, levitation and guidance force characteristics, and the electromagnetic performance of HTS LSM under no-load and load situations are studied with the analysis results are given. Finally, the primary motor running testing results are provided

    Role of TRPM2 in H2O2-induced cell apoptosis in endothelial cells

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    Melastatin-like transient receptor potential channel 2 (TRPM2) is an oxidant-sensitive and cationic non-selective channel that is expressed in mammalian vascular endothelium. Here we investigated the functional role of TRPM2 channels in hydrogen peroxide (H(2)O(2))-induced cytosolic Ca(2+) ([Ca(2+)](i)) elavation, whole-cell current increase, and apoptotic cell death in murine heart microvessel endothelial cell line H5V. A TRPM2 blocking antibody (TM2E3), which targets the E3 region near the ion permeation pore of TRPM2, was developed. Treatment of H5V cells with TM2E3 reduced the [Ca(2+)](i) rise and whole-cell current change in response to H(2)O(2). Suppressing TRPM2 expression using TRPM2-specific short hairpin RNA (shRNA) had similar inhibitory effect. H(2)O(2)-induced apoptotic cell death in H5V cells was examined using MTT assay, DNA ladder formation analysis, and DAPI-based nuclear DNA condensation assay. Based on these assays, TM2E3 and TRPM2-specific shRNA both showed protective effect against H(2)O(2)-induced apoptotic cell death. TM2E3 and TRPM2-specific shRNA also protect the cells from tumor necrosis factor (TNF)-alpha-induced cell death in MTT assay. In contrast, overexpression of TRPM2 in H5V cells resulted in an increased response in [Ca(2+)](i) and whole-cell currents to H(2)O(2). TRPM2 overexpression also aggravated the H(2)O(2)-induced apoptotic cell death. Downstream pathways following TRPM2 activation was examined. Results showed that TRPM2 activity stimulated caspase-8, caspase-9 and caspase-3. These findings strongly suggest that TRPM2 channel mediates cellular Ca(2+) overload in response to H(2)O(2) and contribute to oxidant-induced apoptotic cell death in vascular endothelial cells. Down-regulating endogenous TRPM2 could be a means to protect the vascular endothelial cells from apoptotic cell death.published_or_final_versio

    Slow cooling and efficient extraction of C-exciton hot carriers in MoS2 monolayer

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    In emerging optoelectronic applications, such as water photolysis, exciton fission and novel photovoltaics involving low-dimensional nanomaterials, hot-carrier relaxation and extraction mechanisms play an indispensable and intriguing role in their photo-electron conversion processes. Two-dimensional transition metal dichalcogenides have attracted much attention in above fields recently; however, insight into the relaxation mechanism of hot electron-hole pairs in the band nesting region denoted as C-excitons, remains elusive. Using MoS2 monolayers as a model two-dimensional transition metal dichalcogenide system, here we report a slower hot-carrier cooling for C-excitons, in comparison with band-edge excitons. We deduce that this effect arises from the favourable band alignment and transient excited-state Coulomb environment, rather than solely on quantum confinement in two-dimension systems. We identify the screening-sensitive bandgap renormalization for MoS2 monolayer/graphene heterostructures, and confirm the initial hot-carrier extraction for the C-exciton state with an unprecedented efficiency of 80%, accompanied by a twofold reduction in the exciton binding energy
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